Morbidity and mortality of human newborns are significant public health concerns. Predominant risk factors for neonatal morbidity and mortality are invasive bacterial infections and the ensuing severe inflammatory response, which mainly begin in utero. Group B Streptococci (GBS) are a significant cause of preterm births, stillbirths and early onset neonatal disease. Factors that facilitate ascending GBS infection from the lower genital tract to the fetus are not understood. Our studies indicate that upregulation of virulence factors facilitate GBS invasion of placental membranes in vitro. Using human placental membranes and a nonhuman primate model, the objective of this proposal is to mechanistically define how virulence factors enable ascending in utero GBS infection and subsequent fetal lung and brain injury. PUBLIC HEALTH RELEVANCE: Understanding mechanisms of ascending GBS infection and fetal injury will be beneficial for development of therapeutic strategies against in utero infectios that lead to fetal injury, preterm births, and stillbirths.